Regulation of cutaneous axon regeneration by wound derived H2O2

项目总结（见说明）： 皮肤感觉轴突对损伤的反应再生能力对于恢复组织功能至关重要。尽管它的重要性和许多研究工作在过去，皮肤轴突再生损伤后的机制仍然难以捉摸。我们先前已经发现，小活性氧类过氧化氢（H2O2）是刺激皮肤轴突生长的关键调节分子。历史上，H2O2被视为高浓度时的细胞损伤分子 在细胞中。然而，最近的工作表明，低，无毒浓度的过氧化氢是重要的许多细胞功能的调节。这是通过氧化信号蛋白中的氧化还原敏感性半胱氨酸残基来实现的，最显著的是激酶、磷酸酶和转录因子，这改变了它们的结构和功能。由于H2O2信号传导的研究领域相对较新，因此对其在组织修复过程中的信号传导特性的了解才刚刚开始出现。这一建议的意义在于，它将阐明损伤诱导的H2O2刺激皮肤轴突再生所利用的机制。从这项研究中获得的见解将有助于开发因疾病或创伤而受损的轴突的治疗方法。我们的方法是结合联合收割机体内成像和并行的miRNAs和mRNAs的深度测序来分析躯体感觉神经元中对刺激轴突再生至关重要的H2O2响应遗传网络。

PROJECT SUMMARY (See instructions): The ability to regenerate cutaneous sensory axons in response to injury is crucial for restoring tissue function. Despite its importance and many research efforts in the past, the mechanisms for cutaneous axon regeneration following injury have remained elusive. We have previously discovered that the small reactive oxygen species hydrogen peroxide (H2O2) is a key regulatory molecule for stimulating cutaneous axon growth. Historically, H2O2 has been seen as a cell-damaging molecule, when present at high concentrations in cells. Recent work however, demonstrates that low, non-toxic concentrations of H2O2 are important for regulation of many cellular functions. This is achieved by the oxidation of redox-sensitive cysteine residues in signaling proteins, most notably of kinases, phosphatases, and transcription factors, which alters their structure and function. As the research field of H2O2 signaling is relatively new, insight into its signaling properties during tissue repair is only beginning to emerge. The significance of this proposal is that it will elucidate mechanisms utilized by injury-induced H2O2 that stimulate cutaneous axon regeneration. The insight gained from this research will aid in the development of treatments for damaged axons due to disease or trauma. Our approach is to combine in vivo imaging and parallel deep sequencing of miRNAs and mRNAs to analyze H2O2 responsive genetic networks in somatosensory neurons that are essential for stimulating axon regeneration.